Abstract 6674: Single-dose trilaciclib monotherapy potentiates antitumor immunity in the neoadjuvant setting of triple-negative breast cancer by modulating the composition and effector function of peripheral immune cells
Authors: Sarah Ahn, Subing Cao, Amanda Jacobson, Melissa A. Russo, John S. Yi
Journal: Cancer Research (2023)

Abstract Intravenous administration of trilaciclib transiently arrests cyclin-dependent kinase 4/6-dependent cells in the G1 phase of the cell cycle during chemotherapy exposure. In an open-label, phase 2 study in patients with metastatic triple-negative breast cancer (TNBC; NCT02978716), administering trilaciclib prior to gemcitabine plus carboplatin improved overall survival and resulted in enriched T-cell diversity and decreased clonality in peripheral blood compared with administering chemotherapy alone. This phase 2, single-arm, neoadjuvant study (NCT05112536) aims to determine the immune mechanism of action of trilaciclib and its role in modulating antitumor immune responses in patients with TNBC. Previously untreated patients with early-stage TNBC (N = 24) received single-dose trilaciclib monotherapy during the lead-in phase. After 7 days, patients received systemic therapy with 4 cycles of dose-dense doxorubicin plus cyclophosphamide and 12 weekly cycles of paclitaxel, with trilaciclib administered prior to the first dose of systemic therapy per cycle. Pembrolizumab from cycle 1 and/or carboplatin from cycle 5 was permitted per investigator discretion. Patients underwent curative surgery 3-5 weeks after the last dose of systemic therapy. Peripheral blood samples were collected at baseline, 7 (±1) days post trilaciclib monotherapy prior to chemotherapy, and pre dose on cycle 2, day 1. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples and cryopreserved for immune profiling via cytometry by time-of-flight (CyTOF), and for functional analysis via intracellular cytokine staining (ICS) and dimensionality reduction. A preliminary analysis of PBMCs from 7 patients showed a decrease in peripheral myeloid-derived suppressor cells (MDSCs), monocytes, and classical dendritic cells following single-dose trilaciclib monotherapy. There were nominal changes to the frequency of peripheral CD4+ and CD8+ T cells. In 4/7 patients, trilaciclib monotherapy resulted in increased proportions of activated and polyfunctional CD4+ and CD8+ T cells producing IFNγ, TNFα, and IL-2 cytokines. Furthermore, trilaciclib enhanced the frequency of CD8+ T cells producing granzyme B and perforin. The decrease in MDSCs and increase in functional T cells following trilaciclib monotherapy supports findings from an immune analysis of data from the phase 2 study of trilaciclib in patients with metastatic TNBC. Overall, these data suggest that the transient G1 arrest of peripheral immune cells by single-dose trilaciclib monotherapy favorably modulates immune responses by promoting the generation of polyfunctional T cells and limiting the number of MDSCs in circulation. Enrollment was completed in August 2022. The complete dataset from all 24 patients will be presented. Citation Format: Sarah Ahn, Subing Cao, Amanda Jacobson, Melissa A. Russo, John S. Yi. Single-dose trilaciclib monotherapy potentiates antitumor immunity in the neoadjuvant setting of triple-negative breast cancer by modulating the composition and effector function of peripheral immune cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6674.